Trichlorofluoromethane (CASRN 75-69-4)

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.

STATUS OF DATA FOR Trichlorofluoromethane

File First On-Line 01/31/1987

Category (section)

Status

Last Revised

Oral RfD Assessment (I.A.)

on-line

08/01/1992

Inhalation RfC Assessment (I.B.)

no data

Carcinogenicity Assessment (II.)

no data

_I.
Chronic Health Hazard Assessments for Noncarcinogenic Effects

_I.A.
Reference Dose for Chronic Oral Exposure (RfD)

The oral Reference Dose (RfD) is based on the assumption that thresholds
exist for certain toxic effects such as cellular necrosis. It is expressed
in units of mg/kg-day. In general, the RfD is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily exposure to the human
population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Please refer
to the Background Document for an elaboration of these concepts. RfDs
can also be derived for the noncarcinogenic health effects of substances
that are also carcinogens. Therefore, it is essential to refer to other
sources of information concerning the carcinogenicity of this substance.
If the U.S. EPA has evaluated this substance for potential human carcinogenicity,
a summary of that evaluation will be contained in Section II of this file.

__I.A.2. Principal and Supporting Studies (Oral RfD)

The NCI bioassay was performed on rats and mice exposed to various doses of
trichloromonofluoromethane by gavage over a period of 78 weeks (50
animals/species/sex/dose for each of two doses with 20 animals/species/sex for
each of two control groups). A statistically significant positive association
between increased dosage and accelerated mortality by the Tarone test in male
and female rats and female mice were observed. In treated rats of both sexes
there were also elevated incidences of pleuritis and pericarditis not seen in
controls. Inhalation studies which employed multispecies exposures to higher
levels of the compound than used by NCI (Leuschner et al., 1983) reported no
adverse clinical/pathologic signs of toxicity due to subchronic or short-term
exposures.

The LOAEL of 488 mg/kg/day (based on mortality in rats) was converted to 349
mg/kg/day on a 7-day exposure basis.

__I.A.3.
Uncertainty and Modifying Factors (Oral RfD)

UF — An uncertainty factory of 1000 (10 for LOAEL, 10 for species conversion,
and 10 for sensitive human population), results in an RfD of 0.3 mg/kg/day.

MF — None

__I.A.4.
Additional Studies/Comments (Oral RfD)

None.

__I.A.5.
Confidence in the Oral RfD

Study — Medium
Database — Medium
RfD — Medium

The chosen study is given a medium confidence rating because large numbers of
animals/sex were tested in two doses for chronic exposures, but the study did
not establish a NOEL. The database is given a medium confidence rating
because of the support of chronic data, but the lack of reproductive data.
Medium confidence in the RfD follows.

__I.A.6.
EPA Documentation and Review of the Oral RfD

Source Document — This assessment is not presented in any existing U.S. EPA
document.

Other EPA Documentation — None

Agency Work Group Review — 05/20/1985, 05/31/1985

Verification Date — 05/31/1985

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for Trichlorofluoromethane conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.

__I.A.7.
EPA Contacts (Oral RfD)

Please contact the IRIS Hotline for all questions concerning this
assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX)
or hotline.iris@epa.gov (internet address).

Drinking Water Health Advisories, EPA
Regulatory Actions, and Supplementary Data were removed from IRIS
on or before April 1997. IRIS users were directed to the appropriate
EPA Program Offices for this information.